This phase II trial is studying how well giving bevacizumab together with erlotinib works in treating patients with advanced liver cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and erlotinib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving bevacizumab together with erlotinib may kill more tumor cells

Number of Patients With Confirmed Tumor Response Defined to be Either a Complete Response (CR) or Partial Response (PR). [ Time Frame: Patients were able to continue treatment indefinitely and were evaluated every cycle until discontinued treatment. ] [ Designated as safety issue: No ]

Responses to erlotinib and bevacizumab treatment were evaluated using RECIST Criteria. A Complete Response (CR) is defined as the disappearance of all target lesions. A Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum of the longest diameters.

Secondary Outcome Measures:

Survival Time [ Time Frame: From registration to death due to any cause, patients are followed up to 3 years after treatment ] [ Designated as safety issue: No ]

Survival time is defined as the time from registration to death due to any cause. Estimated using the method of Kaplan-Meier.

Time to Disease Progression [ Time Frame: From registration to documentation of disease progression ] [ Designated as safety issue: No ]

Time to disease progression is defined as the time from registration to documentation of disease progression. Estimated using the method of Kaplan-Meier.

Duration of Response [ Time Frame: The date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented. ] [ Designated as safety issue: No ]

Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented.

Time to Treatment Failure [ Time Frame: From the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal. ] [ Designated as safety issue: No ]

Time to treatment failure is defined to be the time from the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal.

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine EGFR and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by IHC for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, MAPK, and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by ELISA.

III. Determine the levels of vascular endothelial growth factor (VEGF) and VEGF receptors in tumor tissue as well as baseline plasma VEGF levels and correlate these with patient outcome measures.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory studies to determine epidermal growth factor receptor (EGFR) and phosphorylated-EGFR protein levels using initial diagnostic biopsy specimens by immunohistochemistry (IHC) for correlation with clinical outcome. Levels of proteins through which EGFR signals, including Akt, phosphorylated-Akt, mitogen-activated protein kinase (MAPK), and phosphorylated-MAPK, are also determined using initial diagnostic biopsy specimens by IHC and correlated with clinical outcome. Total and free serum vascular endothelial growth factor levels are determined at the start of study and prior to course 3 by enzyme-linked immunosorbent assays (ELISA).

After completion of study treatment, patients are followed periodically for up to 3 years.

No other prior malignancy within the past 5 years except for the following:

Adequately treated basal cell or squamous cell skin cancer; Adequately treated in situ cervical cancer; Stage I or II cancer from which the patient is currently in complete remission; Stage I chronic lymphocytic leukemia

Recovered from all therapy-related toxicities

No more than 1 prior systemic or liver directed drug therapy including transarterial chemoembolization (TACE) (multiple TACEs will count as 1 prior regimen irrespective of their total numbers) that were used for HCC

No chemotherapy for HCC within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)

No biological therapy or immunotherapy for HCC within the past 4 weeks

An in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant (or on a stable dose of low molecular weight heparin)

AND (continued from above) No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels, gastrointestinal [GI] ulceration, or known varices)

No concurrent major surgical procedures

Histologically confirmed hepatocellular carcinoma (HCC):

No fibrolamellar subtype HCC

Advanced disease

Not a candidate for surgical resection or liver transplantation

Measurable disease:

Edges of the indicator lesion must be clearly distinct on CT scan

Lesions that measure at least 1 cm but less than 2 cm only must use spiral CT imaging for both pre- and post-treatment tumor assessments

Child's Pugh classification A or B

No primary brain tumor, brain metastasis, or other CNS diseases

ECOG performance status 0-1

Platelet count >= 75,000/mm^3

No major surgery (e.g., laparotomy), open biopsy, or minor surgery (e.g., insertion of a vascular access device) within the past 4 weeks

No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung

No abdominal fistula, GI perforation, or intra-abdominal abscess within the past 28 days

No concurrent prophylactic hematopoietic colony-stimulating factors

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00365391